Covid-19: features of the pathogenesis of the disease and targets for immunotherapeutic effects

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Abstract

An analysis of current scientific literature on the pathogenesis of the coronavirus infection that caused the 2019 pandemic, COVID-19, was carried out. The structure, genome, introduction into the cell and the life cycle of the SARS-CoV-2 virus that caused the pandemic, the mechanisms of protection of the virus from the host’s immune system, features of the clinical picture of coronavirus infection, the pathogenesis of viral pneumonia, in particular, disruption of the renin-angiotensin system, cytokine storm, participation of the complement system in the pathogenesis of COVID-19 are reviewed. The models of infections caused by SARS-CoV and SARS-CoV-2 in laboratory mice are also considered.

About the authors

N. A. Klimov

Institute of Experimental Medicine

Author for correspondence.
Email: nklimov@mail.ru

PhD (Medicine), Head, Laboratory of Protein Gene Engineering, Department of Medical Biotechnology and Immunopharmacology

Russian Federation, Saint Petersburg, Russia

A. S. Simbirtsev

Institute of Experimental Medicine

Email: simbas@mail.ru

MD, Professor, Corresponding Member of the Russian Academy of Sciences, Head, Department of Medical Biotechnology and Immunopharmacology

Russian Federation, Saint Petersburg, Russia

References

  1. WHO. 2004. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. Available from: https://www.who.int/csr/sars/country/table2004_04_21/en/.
  2. Fehr AR, Channapannavar R, Perlman S. Middle East respiratory syndrome (MERS): Emergence of a pathogenic human Coronavirus. Annu Rev Med. 2017;68:387-399. https://doi.org/10.1146/annurev-med-051215-031152.
  3. Kuhn JH, Li W, Choe H, et al. Angiotensin-converting enzyme 2: A functional receptor for SARS coronavirus. Cell Mol Life Sci. 2004;61(21):2738-2743. https://doi.org/10.1007/s00018-004-4242-5.
  4. Lu R, Zhao X, Li J, et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet. 2020;395(10224):565-574. https://doi.org/10.1016/S0140-6736(20)30251-8.
  5. Kim D, Lee JY, Yang JS, et al. The Architecture of SARS-CoV-2 Transcriptome. Cell. 2020;181(4):914-921.e10. https://doi.org/10.1016/j.cell.2020.04.011.
  6. Li X, Geng M, Peng Y, et al. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10(2):102-108. https://doi.org/10.1016/j.jpha.2020.03.001.
  7. Li W, Moore MJ, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450-454. https://doi.org/10.1038/nature02145.
  8. Hamming I, Timens W, Bulthuis ML, et al. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understand-ding SARS pathogenesis. J Pathol. 2004;203(2):631-637. https://doi.org/10.1002/path.1570.
  9. Walls AC, Park YJ, Tortorici MA, et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;180(2):281-292.e6. https://doi.org/10.1016/j.cell.2020.02.058.
  10. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and Is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.e8. https://doi.org/10.1016/
  11. j.cell.2020.02.052.
  12. Perlman S, Netland J. Coronaviruses post-SARS: Update on replication and pathogenesis. Nat Rev Microbiol. 2009;7(6):439-450. https://doi.org/10.1038/nrmicro2147.
  13. Ogando NS, Dalebout TJ, Zevenhoven-Dobbe JC, et al. SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology. J Gen Virol. 2020;101(9):925-940. https://doi.org/10.1099/jgv.0.001453.
  14. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6):805-820. https://doi.org/
  15. 1016/j.cell.2010.01.022.
  16. Jefferies C. Regulating IRFs in IFN driven disease. Front Immunol. 2019;10:325. https://doi.org/10.3389/fimmu.
  17. 00325.
  18. Mitchell S, Mercado E, Adelaja A, et al. An NFkB activity calculator to delineate signaling crosstalk: Type I and II interferons enhance NFkB via distinct mechanisms. Front Immunol. 2019;10:1425. https://doi.org/10.3389/fimmu.
  19. 01425.
  20. Ivashkiv L, Donlin L. Regulation of type I interferon responses. Nature reviews Immunology. 2014;14(1):36-49. https://doi.org/10.1038/nri3581.
  21. Schoggins J, Wilson S, Panis M, et al. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011;472(7344):481-485. https://doi.org/10.1038/nature09907.
  22. Knoops K, Kikkert M, Worm SH, et al. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum. PLoS Biol. 2008;6(9):e226. https://doi.org/10.1371/journal.pbio.0060226.
  23. Snijder EJ, van der Meer Y, Zevenhoven-Dobbe J, et al. Ultrastructure and origin of membrane vesicles associated with the severe acute respiratory syndrome coronavirus replication complex. J Virol. 2006;80(12):5927-5940. https://doi.org/10.1128/JVI.02501-05.
  24. Li G, Fan Y, Lai Y, et al. Coronavirus infections and immune responses. J Med Virol. 2020;92(4):424-432. https://doi.org/10.1002/jmv.25685.
  25. Totura AL, Baric RS. SARS coronavirus pathogenesis: Host innate immune responses and viral antagonism of interferon. Curr Opin Virol. 2012;2(3):264-275. https://doi.org/10.1016/
  26. j.coviro.2012.04.004.
  27. Kindler E, Thiel V, Weber F. Interaction of SARS and MERS Coronaviruses with the antiviral interferon response. Adv Virus Res. 2016;96:219-243. https://doi.org/10.1016/bs.aivir.2016.08.006
  28. Domingo P, Mur I, Pomar V, et al. The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19). EBioMedicine. 2020;58:102887. https://doi.org/10.1016/j.ebiom.2020.102887.
  29. Blanco-Melo D, Nilsson-Payant B, Liu WC, et al. Imbalanced host response to SARS-CoV-2 drives development of COVID-19. Cell. 2020;181(5):1036-1045.e9. https://doi.org/10.1016/j.cell.2020.04.026.
  30. Lokugamage K, Hage A, Schindewolf C, et al. SARS-CoV-2 is sensitive to type I interferon pretreatment. bioRxiv. 2020;2020.03.07.982264. https://doi.org/10.1101/2020.03.07.982264.
  31. Faure E, Poissy J, Goffard A, et al. Distinct immune response in two MERS-CoV-infected patients: Can we go from bench to bedside? PLoS One. 2014;9(2):e88716. https://doi.org/10.1371/journal.pone.0088716.
  32. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529-539. https://doi.org/10.1007/s00281-017-0629-x.
  33. Channappanavar R, Fehr A, Vijay R. et al. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe. 2016;19(2):181-193. https://doi.org/10.1016/j.chom.2016.01.007.
  34. Gu J, Gong E, Zhang B, et al. Multiple organ infection and the pathogenesis of SARS. J Exp Med. 2005;202(3):415-424. https://doi.org/10.1084/jem.20050828.
  35. Huang K, Su IJ, Theron M, et al. An interferon-gamma-related cytokine storm in SARS patients. J Med Virol. 2005;75(2):185-194. https://doi.org/10.1002/jmv.20255.
  36. Cameron M, Xu L, Danesh A, et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol. 2007;81(16):8692-8706. https://doi.org/10.1128/JVI.00527-07.
  37. Hadjadj J, Yatim N, Barnabei L, et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020;369(6504):718-724. https://doi.org/10.1126/science.abc6027.
  38. Paranjpe I, Russak A, De Freitas JK, et al. Clinical characteristics of hospitalized COVID-19 patients in New York City. medRxiv. 2020;2020.04.19.20062117. https://doi.org/10.1101/2020.04.19.20062117.
  39. Zhu J, Zhong Z, Ji P, et al. Clinicopathological characteristics of 8697 patients with COVID-19 in China: A meta-analysis. Fam Med Commun Health. 2020;8(2):e000406. https://doi.org/10.1136/fmch-2020-000406.
  40. Kuba K, Imai Y, Rao S, et al. Lessons from SARS: Control of acute lung failure by the SARS receptor ACE2. J Mol Med (Berl). 2006;84(10):814-820. https://doi.org/10.1007/s00109-006-0094-9.
  41. Chen J, Subbarao K. The immunobiology of SARS. Annu Rev Immunol. 2007;25(1):443-472. https://doi.org/10.1146/annurev.immunol.25.022106.141706.
  42. Cheung OY, Chan JW, Ng CK, et al. The spectrum of pathological changes in severe acute respiratory syndrome (SARS). Histopathology. 2004;45(2):119-124. https://doi.org/10.1111/j.1365-2559.2004.01926.x.
  43. Zhang ZL, Hou YL, Li DT, et al. Laboratory findings of COVID-19: A systematic review and meta-analysis. Scand J Lab Invest. 2020;80(6):441-447. https://doi.org/10.1080/00365513.2020.1768587.
  44. Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581(7809):465-469. https://doi.org/10.1038/s41586-020-2196-x.
  45. Mehta PK, Griendling KK. Angiotensin II cell signaling: Physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol. 2007;292(1):C82-97. https://doi.org/10.1152/ajpcell.00287.2006.
  46. Simões e Silva AC, Silveira KD, Ferreira AJ, et al. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis. Br J Pharmacol. 2013;169(3):477-492. https://doi.org/10.1111/bph.12159.
  47. Patel VP, Zhong J-C, Grant MB, et al. Role of the ACE2/Angiotensin 1-7 axis of the renin-angiotensin system in heart failure. Circ Res. 2016;118(8):1313-1326. https://doi.org/10.1161/CIRCRESAHA.116.307708.
  48. Imai Y, Kuba K, Rao S, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436(7047):112-116. https://doi.org/10.1038/nature03712.
  49. Kuba K, Imai Y, Rao S, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11(8):875-879. https://doi.org/10.1038/nm1267.
  50. Liu Y, Yang Y, Zhang C, et al. Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury. Sci China Life Sci. 2020;63(3):364-374. https://doi.org/10.1007/s11427-020-1643-8.
  51. Fara A, Mitrev Z, Rosalia RA, Cytokine storm and COVID-19: A chronicle of proinflammatory cytokines. Open Biol. 2020;10(9):200160. https://doi.org/10.1098/rsob.200160.
  52. Johnson BS, Laloraya M. A cytokine super cyclone in COVID-19 patients with risk factors: The therapeutic potential of BCG immunization. Cytokine Growth Factor Rev. 2020;54:32-42. https://doi.org/10.1016/j.cytogfr.2020.06.014.
  53. Ruan Q, Yang K, Wang W, et al. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020;46(5):846-848. https://doi.org/10.1007/s00134-020-05991-x.
  54. Herold T, Jurinovic V, Arnreich C, et al. Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19. J Allergy Clin Immunol. 2020;146(1):128-136.e4. https://doi.org/10.1016/j.jaci.2020.05.008.
  55. Симбирцев А.С. Цитокины в патогенезе и лечении заболеваний человека. – СПб.: Фолиант, 2018. – 510 с. [Simbirtsev AS. Tsitokiny v patogeneze i lechenii zabolevanii cheloveka. Saint Petersburg: Foliant; 2018. 510 р. (In Russ.)]
  56. Wang W, Ye L, Ye L, et al. Up-regulation of IL-6 and TNF-alpha induced by SARS-coronavirus spike protein in murine macrophages via NF-kappaB pathway. Virus Res. 2007;128(1-2):1-8. https://doi.org/10.1016/j.virusres.
  57. 02.007.
  58. Zhang X, Wu K, Wang D, et al. Nucleocapsid protein of SARS-CoV activates interleukin-6 expression through cellular transcription factor NF-kappaB. Virology. 2007;365(2):324-335. https://doi.org/10.1016/j.virol.2007.04.009.
  59. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. https://doi.org/10.1016/S0140-6736(20)30183-5.
  60. Soy M, Keser G, Atagündüz P, et al. Cytokine storm in COVID-19: Pathogenesis and overview of anti-inflammatory agents used in treatment. Clin Rheumatol. 2020;39(7):2085-2094. https://doi.org/10.1007/s10067-020-05190-5.
  61. Sarzi-Puttini P, Giorgi V, Sirotti S, et al. COVID-19, cytokines and immunosuppression: What can we learn from severe acute respiratory syndrome? Clin Exp Rheumatol. 2020;38(2):337-342.
  62. Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-1418. https://doi.org/10.1016/S0140-6736(20)30937-5.
  63. Magro C, Mulvey CJ, Berlin D, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases. Transl Res. 2020;220:1-13. https://doi.org/10.1016/j.trsl.2020.04.007.
  64. Laurence J, MulveyJJ, Seshadri M, et al. Anti-complement c5 therapy with eculizumab in three cases of critical COVID-19. Clin Immunol. 2020;219:108555. https://doi.org/10.1016/j.clim.2020.108555.
  65. Rambaldi A, Gritti G, Micò MC, et al. Endothelial injury and thrombotic microangiopathy in COVID-19: Treatment with the lectin-pathway inhibitor narsoplimab. Immunobiology. 2020;9:152001. https://doi.org/10.1016/j.imbio.2020.152001.
  66. Gralinski LE, Sheahan TP, Morrison TE, et al. Complement activation contributes to severe acute respiratory syndrome coronavirus pathogenesis. mBio. 2018;9(5):e01753-18. https://doi.org/10.1128/mBio.01753-18.
  67. Diurno F, Numis FG, Porta G, et al. Eculizumab treatment in patients with COVID-19: Preliminary results from real life ASL Napoli 2 Nord experience. Eur Rev Med Pharmacol Sci. 2020;24(7):4040-4047. https://doi.org/10.26355/eurrev_202004_20875.
  68. Mastaglio S, Ruggeri A, Risitano AM, et al. The first case of COVID-19 treated with the complement C3 inhibitor AMY-101. Clin Immunol. 2020;215:108450. https://doi.org/10.1016/j.clim.2020.108450.
  69. Du L, He Y, Zhou Y, et al. The spike protein of SARS-CoV — a target for vaccine and therapeutic development. Nat Rev Microbiol. 2009;7(3):226-236. https://doi.org/10.1038/nrmicro2090.
  70. Yasui F, Kohara M, Kitabatake M, et al. Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus. Virology. 2014;454-455:157-168. https://doi.org/10.1016/j.virol.2014.02.005.
  71. Ni L, Ye F, Cheng ML, et al. Detection of SARS-CoV-2-Specific humoral and cellular immunity in COVID-19 convalescent individuals. Immunity. 2020;52(6):971-977.e3. https://doi.org/10.1016/j.immuni.2020.04.023.
  72. Gong SR, Bao LL. The battle against SARS and MERS coronaviruses: Reservoirs and animal models. Animal Model Exp Med. 2018;1(2):125-133. https://doi.org/10.1002/ame2.12017.
  73. Roberts A, Paddock C, Vogel L, et al. Aged BALB/c mice as a model for increased severity of severe acute respiratory syndrome in elderly humans. J Virol. 2005;79(9):5833-5838. https://doi.org/10.1128/JVI.79.9.5833-5838.2005.
  74. Day СW, Baric R, Cai SX, et al. A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo. Virology. 2009;395(2):210-222. https://doi.org/10.1016/j.virol.2009.09.023.
  75. Roberts A, Deming D, Paddock CD, et al. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. PLoS Pathog. 2007;3(1):e5. https://doi.org/10.1371/journal.ppat.0030005.
  76. Yang XH, Deng W, Tong Z, et al. Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. Comp Med. 2007;57(5):450-459.
  77. Bao L, Deng W, Huang B, et al. The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice. Nature. 2020;583(7818):
  78. -833. https://doi.org/10.1038/s41586-020-2312-y.
  79. McCray PB, Pewe L, Wohlford-Lenane C, et al. Lethal Infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol. 2007;81(2):813-821. https://doi.org/10.1128/JVI.02012-06.
  80. Jiang RD, Liu MQ, Chen Y, et al. Pathogenesis of SARS-CoV-2 in transgenic mice expressing human angiotensin-converting enzyme 2. Cell. 2020;182(1):50-58.e8. https://doi.org/10.1016/j.cell.2020.05.027.
  81. Lutz C, Maher L, Lee C, et al. COVID-19 preclinical models: Human angiotensin-converting enzyme 2 transgenic mice. Hum Genomics. 2020;14(1):20. https://doi.org/10.1186/s40246-020-00272-6.
  82. Yuen CK, Lam JY, Wong WM, et al. SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists. Emerg Microbes Infect. 2020;9(1):1418-1428. https://doi.org/10.1080/22221751.2020.1780953.
  83. Omrani A, Saad M, Baig K, et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: A retrospective cohort study. Lancet Infect Dis. 2014;14(11):1090-1095. https://doi.org/10.1016/S1473-3099(14)70920-X.
  84. Zumla A, Chan J, Azhar E, et al. Coronaviruses – drug discovery and therapeutic options. Nat Rev Drug Discov. 2016;15(5):327-347 https://doi.org/10.1038/nrd.2015.37.
  85. Park A, Iwasaki A. Type I and type III interferons – induction, signaling, evasion, and application to combat COVID-19. Cell Host Microbe. 2020;27(6):870-878. https://doi.org/10.1016/j.chom.2020.05.008.
  86. Dong L, Hu S, Gao J. Discovering drugs to treat coronavirus disease 2019 (COVID-19). Drug Discov Ther. 2020;14(1):58-60. https://doi.org/10.5582/ddt.2020.01012.
  87. WHO. Draft landscape of COVID-19 candidate vaccines. Available from: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines.
  88. Usmani SS, Raghava GP. Potential challenges for coronavirus (SARS-CoV-2) vaccines under trial. Front Immunol. 2020;11:561851. https://doi.org/10.3389/fimmu.2020.561851.
  89. Tseng CT, Sbrana E, Iwata-Yoshikawa N, et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One. 2012;7(4):e35421. https://doi.org/10.1371/journal.pone.0035421.
  90. Sajna KV, Kamat S. Antibodies at work in the time of severe acute respiratory syndrome coronavirus 2. Cytotherapy. 2020;S1465-3249(20)30846-X. https://doi.org/10.1016/j.jcyt.2020.08.009.
  91. Owji H, Negahdaripour M, Hajighahramani N. Immunotherapeutic approaches to curtail COVID-19. Int Immunopharmacol. 2020;88:106924. https://doi.org/10.1016/
  92. j.intimp.2020.106924.
  93. ClinicalTrials.gov. Explore 358,767 research studies in all 50 states and in 219 countries. Available from: www.clinicaltrials.gov.
  94. Liu P, Wysocki J, Souma T, et al. Novel ACE2-Fc chimeric fusion provides long-lasting hypertension control and organ protection in mouse models of systemic renin angiotensin system activation. Kidney Int. 2018;94(1):114-125. https://doi.org/10.1016/j.kint.2018.01.029.
  95. Moore MJ, Dorfman T, Li W, et al. Retroviruses pseudotyped with the severe acute respiratory syndrome coronavirus spike protein efficiently infect cells expressing angiotensin-converting enzyme 2. J Virol. 2004;78(19):10628-10635. https://doi.org/10.1128/JVI.78.19.10628-10635.2004.
  96. Li Y, Wang H, Tang X, et al. SARS-CoV-2 and three related coronaviruses utilize multiple ACE2 orthologs and are potently blocked by an improved ACE2-Ig.
  97. J Virol. 2020;94(22):e01283-20. https://doi.org/10.1128/JVI.01283-20.
  98. Wang X, Mathieu M, Brezski RJ. IgG Fc engineering to modulate antibody effector functions. Protein Cell. 2018;9(1):63-73. https://doi.org/10.1007/s13238-017-0473-8.
  99. Iwanaga N, Cooper L, Rong L, et al. Novel ACE2-IgG1 fusions with improved activity against SARS-CoV2. bioRxiv. 2020;2020.06.15.152157. https://doi.org/10.1101/2020.06.
  100. 152157.
  101. Hussen J, Kandeel M, Hemida MG, Al-Mubarak AI. Antibody-based immunotherapeutic strategies for COVID-19. Pathogens. 2020;9(11):E917. https://doi.org/10.3390/pathogens9110917.
  102. Wooding DJ, Bach H. Treatment of COVID-19 with convalescent plasma: Lessons from past coronavirus outbreaks. Clin Microbiol Infect. 2020;26(10):1436-1446. https://doi.org/10.1016/j.cmi.2020.08.005.
  103. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology. Semin Immunopathol. 2017;39(5):529-539. https://doi.org/10.1007/s00281-017-0629-x.

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